All you crash dieters must have experienced an insane craving to bite into a huge bar of sugar-free chocolate or down a can of diet soda but still not felt completely satiated after having these foods! If we cannot derive the required nutrition in terms of calories from sugar, our brain will not send out the satiety signal for us to stop eating.

A recent study on the fruit fly ‘drosophila’ has revealed that the probable reason as to why we can taste the sweetness of artificial sugar but not get the sugar high might be a hormonal circuit in our body which can distinguish between real sugar and artificial sweeteners.

Monica Dus, Assistant Professor currently at the U-M Department of Molecular, Cellular and Developmental Biology and the first author on the paper has identified a brain-gut microcircuit in the fly with a nutrient sensor that can detect the nutritive value of exogenous sugar independent of its sweetness. Published in the journal Neuron, the research has revealed the cellular and molecular nature of the nutrient sensor. The sensor was shown to be composed of six neurosecretory cells secreting diuretic hormone 44 (Dh44) which is the insect homolog of the mammalian corticotropin-releasing hormone (CRH).

Professor Dus states that there is a 75% overlap between the disease causing genes in drosophila and humans. Also the homology between Drosophila Dh44 and mammalian CRH is approximately 30%. This indicates that there is a functional conservation of the two systems. Dus said “We can ask, ‘Do these genes work the same in humans, to tell real sugar from artificial sweetener? The bits and pieces are there, so it is really possible that these genes work in a similar way. Plus, we knew that the human brain could tell the difference between real and fake sugar, we just did not know how.”

The study demonstrates how the choice of nutritive sugar, the one which provides energy upon ingestion over artificial sweetener is related to a feedback energy mechanism. The researchers prompted food-deprived fruit flies to choose between artificial non-nutritive sweeteners, diet sweetener and real sugar. The flies chose real sugar over the diet and artificial sweeteners independent of taste and upon its ingestion, the release of Dh44 hormone was stimulated. Dh44 was responsible for conveying the signal from Dh44 neurons to their receptors R1 in the brain and R2 in the gut.

The researchers tested 3 types of nutritive sugars which specifically activated Dh44 namely, D-glucose, D-trehalose, and D-fructose. As the blood sugar level rose, a positive feedback loop was activated which led to the flies consuming more nutritive sugar as an energy source. This response was not activated on consumption of artificial sweeteners since their metabolism doesn’t provide energy.

Previously, Dus and her team had also demonstrated that the flies can choose nutritive sugars over artificial sweeteners even in the dark and also without being able to taste them. This clearly underscores the importance of the caloric energy provided by the sugars that helps the flies distinguish between real sugar and artificial sweeteners.

The study describes two types of mechanisms for making a food choice – a ‘post ingestive’ response which can detect the D-glucose nutritional value depending on the rise in postprandial glycemia and a ‘hunger’ response which gauges the level of energy in the body and prompts D-glucose consumption after being deprived of food for extended periods. It was also worth noting that Dh44 was responsible not only for participating in the detection of nutritional sugar content but also for coordinating the ingestion and digestion of sugar.

Although the human brain is much more complex and possesses 86 billion neurons as opposed to 100,000 in drosophila, the neurosecretory circuit is similarly located in humans as in the fly which makes it easier to explore the area further.

The researchers would like to further investigate whether the CRH neurons present in mammals can mediate the same glucose sensor effect as in drosophila. The study thus highlights the fact that artificial sweeteners might be soothing to the craving taste buds but will not be able to satisfy the hunger pangs which only real sugar can!